Figura 1. Macroscopy: hepatic segment with solid-cystic lesion in segment VII.

Figura 2. a. Solid-cystic biliary. Papillary intraductal biliary neoplasm. b. Presence of papillary ...

Figura 3. Intraductal neoplasia with low-grade dysplasia in adjacent intrahepatic ducts. H&E, 20x or...

Figura 4. a. CK7 positive in IPNB. b. P53 positivity IPNB cores.

Introduction

Intraductal papillary neoplasm of the bile duct (IPNB) is a high-risk preneoplastic lesion that is uncommon in our environment.

In 2010, the World Health Organization (WHO) introduced the term IPNB and incorporated it into the classification of bile duct tumors1.

IPNB was first described in 1894 by Chapet, and imaging studies constitute an essential pillar in the diagnosis and the clinical-surgical management of these infrequent entities1-4.

IPNB is characterized by papillary neoplastic proliferation that can affect both the intrahepatic and extrahepatic bile ducts3. It is considered the counterpart of papillary neoplasms of the pancreas and has been associated with hepatolithiasis, sclerosing cholangitis, congenital anomalies, and parasitosis4,5. The lesion may be associated with invasive carcinoma in 40 to 80% of cases, emphasizing the importance of early diagnosis6.7.

The clinical features are non-specific, making preoperative diagnosis challenging6-8. The recommended treatment is surgery, and in cases of extensive involvement, liver transplantation becomes an option9,10. Here, we present a case of a patient with abdominal pain, suspected IPNB, and a histopathological diagnosis of IPNB at our institution.

Clinical case

A 67-year-old female patient presented with abdominal pain. During physical examination she reported tenderness upon palpation in the right hypochondrium. On admission, a computed tomography (CT) scan revealed a cystic lesion measuring 36 x 25 mm with a solid, vegetating, and irregular component that enhanced after contrast administration. In addition, the magnetic resonance imaging (MRI) showed a lesion in the VII hepatic segment with lobulated contours, distinct borders, and measuring 32 mm at its widest diameter.

In the distal posterosuperior subcapsular hepatic parenchyma of segment VII, mild bile duct dilation and signs of chronic biliary stasis were observed. The imaging appearance suggested a potential diagnosis of IPNB. Based on this diagnostic suspicion, a left hepatectomy was performed, and the surgical specimen was send for histopathological study.

Macroscopic examination revealed a cystic area containing solid, friable, brownish-brown material with a soft consistency (Figure 1).

Histopathology showed the presence of papillary projections, characterized by thin connective-vascular axes and lined with gastric, biliary, and intestinal epithelium with areas of low- and high-grade dysplasia, but without an invasive component (Figures 2 and 3). The cells tested positive for monoclonal antibodies for CK7 and P53 (Figures 4a and b). The surgical margins were lesion free.

The diagnosis was confirmed as IPNB with epithelial dysplasia, and no evidence of associated invasive carcinoma was found.

The patient was discharged 5 days after surgery, and at the time of this presentation no disease recurrence was observed.

Discussion

Here we describe the clinical case of a patient presenting with abdominal pain and suspected IPNB based on imaging findings, leading to a hepatic segmentectomy. The histopathological analysis showed a Type 1 IPNB with gastric and intestinal epithelium with both low- and high-grade epithelial dysplasia.

Intraductal papillary neoplasm of the bile duct, included in the WHO classification of the bile duct tumors, establishes a new paradigm in the diagnosis of cystic liver lesions. With the availability of imaging methods, early diagnosis of non-lithiasic biliary obstruction can be achieved, enabling prompt surgical intervention with the potential to prevent progression to adenoma-carcinoma, which may occur in these lesions1.

The entity was initially described by Chapet and its most common symptoms are abdominal pain, cholangitis, and jaundice; however, it can also be asymptomatic1-4. In our case, the patient’s primary complaint was hypochondrial pain.

Bile duct tumors are estimated to occur in 7% to 38% and have been referred to by different names such as biliary papillomatosis and intraductal mucinous papillary neoplasia of the bile duct5-7. The entity comprises a heterogeneous group of lesions with varying morphology and clinicopathological characteristics and different prognoses8-13.

IPNB is defined as an epithelial neoplasm characterized by the formation of papillary structures within the intrahepatic and extrahepatic bile ducts, resulting in luminal obstruction and subsequent dilation of the biliary tract1,3,4. It has considerable morphological diversity, ranging from dilated or cystic ducts to mural or exophytic papillary growth, associated with variable epithelial composition and degree of dysplasia. The type of epithelium is related to the degree of dysplasia and the likelihood of invasive carcinoma1,7,8.

Histopathologically, four epithelial subtypes like the pancreatic intraductal version (pancreato-biliary, intestinal, gastric, and oncocytic) are recognized, with the pancreato-biliary type being the most frequent.

The progression from low-grade dysplasia to high-grade and invasive carcinoma follows the adenoma-cancer sequence. This progression is related to the acquisition of genetic alterations, including mutations in the KRAS and P53 genes, and loss of P167-9.

In the study conducted by the Japan Biliary Association (JBA) and Korean Association of Hepato-Biliary-Pancreatic Surgery (KAHBPS), IPNB were classified into two subtypes, which were subsequently incorporated into the WHO classification10-13. Type 1 refers to the intrahepatic location, while type 2 refers to the extrahepatic location, with distinct epithelial characteristics and associations with cancer. Type 2, characterized by biliopancreatic/intestinal epithelium, is associated with carcinoma in 71 to 94% of cases. The most frequent location for this entity is within the intrahepatic biliary tract7,8.

In a large study by Yeh et al. it was found that 46% of the patients with IPNB had progressed to invasive carcinoma at the time of diagnosis, while the loco-regional recurrence rate reached 40-70% at five years in cases of malignant transformation14.

In the series by Choi et al. the recurrence rate in intrahepatic locations was 16%, with an overall 3-year survival rate of 77.6%, and of 62.5% in cases of invasive carcinoma15.

When IPNB is suspected based on clinical and imaging findings, surgical treatment should be considered, with or without resection of the extrahepatic biliary tract. In cases of bilateral involvement, liver transplantation should be proposed if feasible15-17.

Better prognosis and higher survival rates are associated with early diagnosis and resection, as well as with type 1 IPNB, as reported in other series14,15.

Conclusion

Our communication of a case of IPNB aims to raise awareness and extend the knowledge of these rare entities in our country. Due to their high potential for malignancy, it is important to consider these entities among the cystic liver lesions and use the diagnostic expertise of a multidisciplinary team, as early diagnosis and treatment are crucial to improve the survival of patients with this condition.

Intellectual property. The authors declare that the data and figures in the manuscript are original and were produced at their institutions.

Acknowledgments: J. Deurloo for editing assistance.

1. Chapet V. Cancer epitelial primitive du canal coledoque. Lyon Medical 1894;76:145.

2. World Health Organization; Intraductal papillary neoplasm of the bile ducts. In: WHO Classification of Tumours. 5th ed. Lyon, France, IARC,2020.

3. Barton JG, Barrett DA, Maricevich MA, et al. Intraductal papillary mucinous neoplasm of the biliary tract: A real disease? HPB (Oxford) 2009;11:684-91.

4. Ohtsuda M, Kimura F, Shimizuet H, et al. Similarities and differences between intraductal papillary tumors of the bile duct with or without macroscopically visible mucin secretion. Am J Surg Pathol 2011;35:512-21.

5. Gordon-Weeks AN, Jones K, Harriss E, Smith A, Silva M. Systematic Review and Meta-analysis of Current Experience in Treating IPNB: Clinical and Pathological Correlates. Ann Surg 2016;263:656-63.

6. Wan XS, Xu YY, Qianet JY, et al. Intraductal papillary neoplasm of the bile duct. World J Gastroenterol 2013;19:8595-8604.

7. Kim JR, Lee KB, Kwon W, Kim E, Kim SW, Janget JY. Characteristics of Intraductal Papillary Neoplasm of Bile duct according to Morphological and Anatomic classifications. J Korean Med Sci 2018;33:e266.

8. Kim JR, Jang KT, Janget JY, al, Clinicopathological analysis of intraductal papillary neoplasm of bile duct: Korean multicenter cohort study. HPB (Oxford) 2020;22:1139-48.

9. Kim KM, Lee JK, Shin JU, et al. Clinicopathologic features of intraductal papillary neoplasm of the bile duct according to histopathological subtype. Am J Gastroenterol 2012;107:118-25.

10. Nakanuma Y, Kakuda Y, Uesaka K. Characterization of Intraductal Papillary Neoplasm of the Bile Duct with repect to the Histopathologic Similarities to Pancreatic Intraductal Papillary Mucinous Neoplasm. Gut Liver 2019;13:617-27.

11. Kubota K, Jang JY, Nakanuma Y, et al. Clinicopathological characteristics of intraductal papillary neoplasm of the bile duct: a Japan-Korea collaborative study. J Hepatobiliary Hepatobiliary Pancreat Sci 2020;27:581-97.

12. Nakanuma Y, Uesaka K, Kakuda Y, et al. Intraductal Papillary Neoplasm of Bile Duct: Updated Clinicopathological Characteristics and Molecular and Genetic Alterations. J Clin Med 2020;9:3991.

13. Yeh TS, Tseng JH, Chen TC, et al, Characterization of intrahepatic cholangiocarcinoma of the intraductal growth-type and its precursor lesions. Hepatology 2005;42:657-64.

14. Choi SC, Lee JK, Jung JH, et al. The clinicopathological features of biliary intraductal papillary neoplasms according to the location of tumors. J Gastroenterol Hepatol 2010;25:725-30.

15. Jung G, Park KM, Lee SS, Yu E, Hong SM, Kimet J. Long term clinical outcome of the surgically resected intraductal papillary neoplasm of the bile duct. J Hepatology 2012;57:787-93.

16. Caso-Maestro O, Justo Alonso I, Rodríguez Gil Y, Marcacuzco Quinto A, Calvo Pulido J, Jiménez Romero C. La papilomatosis biliar difusa puede recidivar después del trasplante hepático en ausencia de carcinoma infiltrante. Rev Esp Enferm Dig 2018;110:526-8.

17. Matsumoto T, Kubota K, Hachiya H, et al. Impact of Tumor Location on Postoperative Outcome of Intraductal Papillary Neoplasm of the Bile Duct. World J Surg 2019;43:1313-22.

Para descargar el PDF del artículo
Intraductal papillary neoplasm of the bile duct: case presentation and review of the literature

Haga click aquí